During development the proper spacial and temporal development of the vasculature is of fundamental importance to normal morphogenesis. During craniofacial development, aberrant vasculature has been suggested to be causally related in the etiology of a number of congenital anomalies (Poswillo, 1975; Gregg and Avery, 1971). Does the vasculature furnish developmental cues which modulate or are permissive to cell differentiation during organogenesis? Using cortisone acetate and triamcinolone acetate to treat A/Jax mice and chick embryos to produce craniofacial anomalies we will investigate the patterns and the functionality (permeability, ionic composition of blood, integrity of the capillaires) of the developing vasculature and determine the relation of the vasculature to organogenesis will be examined using the chick chorioallantoic membrane grafting technique for explanting tissues, as a bioassay for the differentiation and morphogenesis of the limb and the formation of endochondral bone in a vascular and avascular environment. Inhibitors of vascular gorwth, which are present in cartilage and avascular tissue, will be purified and their effect on endothelial cell proliferation and metabolism will be investigated. These studies will provide an understanding of the role of the vasculature in development, and its relation to craniofacial anomalies. They will also provide an insight into the mechanisms of cell-cell interaction and communication related to the development of the vasculature vis-a-vis organogenesis. These investigations are an imperative prerequisite to the understanding and prevention of craniofacial anomalies.